CHF Treatment: Is Furosemide on the Way Out?

"Furosemide is good for filling the patient’s bladder, but the patient probably did not call for help filling his/her bladder." —Rogue Medic

Nitro, morphine and furosemide: they’ve been the Holy Trinity of emergent treatment of acute CHF since the 1960s, but does the pulmonary edema cocktail actually work? Recent advances in our understanding and treatment of acute congestive heart failure and acute pulmonary edema may spell the doom of prehospital administration of furosemide.

Epidemiology

Congestive heart failure is one of the most prevalent forms of cardiac disease in the United States. Nearly 5 million Americans have the disease, and an additional 500,000 are diagnosed each year. It is the most common cause of hospitalizations in patients over age 65, and half of those diagnosed will be dead within five years. Each year 300,000 people die of the disease, and care for CHF patients represents 3–5% of the total U.S. healthcare budget.¹ With the aging of the baby boomers and the resultant graying of America, those numbers will continue to rise.

Pathophysiology

Congestive heart failure (CHF) is a complex disease process, comprised of four distinct clinical syndromes: acute pulmonary edema, hypertensive crisis, cardiogenic shock and chronic heart failure. While all four will frequently be encountered by prehospital providers, rarely will chronic heart failure require prehospital intervention, unless exacerbation of chronic CHF manifests itself as one of the other clinical syndromes. For the purposes of this article, we will limit most of our discussion to the treatment of acute pulmonary edema.

Distilled to its essence, CHF is simply cardiac output insufficient to meet the demands of the body. It may manifest itself as right heart failure, in which a damaged right ventricle results in decreased blood flow to the lungs and backup of blood in the venous system, or it may manifest itself as left heart failure, resulting in impaired arterial blood flow and backup of blood in the pulmonary circulation. Mixed presentations are also common. It can develop over time as a chronic disease state or it may occur rapidly as a result of an acute disease process, such as severe sepsis or myocardial infarction.

Edema can result from one of two causes: increased capillary permeability or increased hydrostatic pressure. Edema resulting from increased capillary permeability, such as third-spacing from sepsis, is generally of a non-cardiogenic cause, and is beyond the scope of this article. Acute respiratory distress syndrome (ARDS) is an example. However, edema from increased hydrostatic pressure within the microvasculature usually results from a cardiogenic cause, i.e., CHF. If the increased pressure is in the venous system (right heart failure), plasma accumulates in the tissues, manifesting itself as peripheral edema and, if serious, in distended jugular veins and ascites. If the increased pressure is in the pulmonary vasculature, plasma accumulates in the extravascular pulmonary tissues, manifesting itself as pulmonary edema.

Whatever the cause, CHFers rarely call EMS because their feet are swollen. They call because they can’t breathe, which is why we have traditionally considered CHF a cardiac disease disguised as a respiratory condition. The bulk of prehospital treatment of CHF is aimed at treating the primary clinical manifestation of left heart failure: cardiogenic acute pulmonary edema (APE).

Acute Pulmonary Edema

The most common cause of cardiogenic APE is cardiac dysfunction—a dysrhythmia, valvular insufficiency or damage to the left ventricle, which may be chronic or acute. Chronic CHF is characterized by significant changes in the left ventricle’s structure, leading to problems with cardiac output and ejection fraction. These in turn cause a backup in the pulmonary circulation due to the left ventricle’s inability to pump blood forward, leading to an increase in hydrostatic pressure in the pulmonary circulation.¹

Normally, fluid stays in the vascular space because of a balance between hydrostatic pressure (pumping pressure) and osmotic pull generated by plasma proteins and other dissolved particles in the blood. When hydrostatic pressure increases so that the balance is overcome, plasma is forced outward across the alveolar-capillary membrane into the interstitial space, resulting in increased alveolar- capillary distance and impaired diffusion of respiratory gases. Hypoxemia and hypercapnea soon follow.

Clinical presentation of acute pulmonary edema almost always manifests itself as severe respiratory distress, often accompanied by a constellation of associated signs and symptoms, including:

• Profound hypertension (hallmark sign).
• Paroxysmal nocturnal dyspnea.
• Orthopnea.
• Exaggerated air hunger.
• Diaphoresis.
• Chest pain or tightness.
• An S₃ heart sound.
• Adventitious lung sounds, such as crackles or wheezes.
• Cyanosis or pallor.

Prehospital Treatment of APE

Treatment of acute pulmonary edema in past years has focused on dilatation of peripheral vasculature to improve venous capacitance and decrease peripheral arterial vascular resistance, and removal of the excess fluid through diuresis. The three pharmacologic agents traditionally used to accomplish this are nitroglycerine, morphine sulfate and a loop diuretic, such as furosemide (Lasix).

Ultimately, the goal of vasodilation is to reduce left ventricular preload. Nitroglycerine in low doses effectively dilates the venous system, resulting in increased venous capacitance and reduced blood return to the right ventricle. This reduction in right ventricular preload, in turn, results in less blood flow through the pulmonary vascular bed, and ultimately, less outflow to the left ventricle. This reduction in left ventricular preload allows for the damaged left ventricle to more closely match stroke volume to ventricular filling. The end result is decreased hydrostatic pressure in the pulmonary vasculature and less congestion.

However, it also became apparent that higher doses of nitroglycerine resulted in significant dilation of the arterial system as well, reducing peripheral vascular resistance, increasing forward flow and, ultimately, decreasing workload for the weak and damaged left ventricle. This global vasodilatory effect of nitroglycerine has been shown to significantly reduce mortality in APE patients treated in the prehospital setting, and even hypotensive patients (systolic BP < 100) were shown to benefit from intravenous nitroglycerine.²

Morphine sulfate, the second pharmacologic arm of traditional CHF treatment, was long thought to aid in vasodilation while simultaneously decreasing the anxiety common in APE patients, but recent studies indicate that the vasodilatory effects of morphine are transient and frequently overstated.³ Moreover, the vasodilation from morphine is histamine-mediated, and the increased capillary permeability—particularly in the pulmonary vasculature—common with histamine release may be detrimental to the patient in acute CHF. Many clinicians are also concerned with morphine’s potential for CNS and respiratory depression in the acute CHF patient. One retrospective study of APE patients treated in the ED found a significant increase in the number of intubations and ICU admissions in patients who received morphine versus those who were administered sublingual captopril.⁴

Furosemide is a loop diuretic that inhibits sodium reabsorption in the ascending loop of Henle and the distal convoluted tubules of the renal medulla. Following the principle that “water follows salt,” this increased sodium content in the collecting tubules resulted in increased water excretion from the kidneys.

Once pulmonary vascular pressure was decreased through vasodilation with nitroglycerine and morphine, it was considered necessary to remove the excess fluid via diuresis with furosemide. Many texts still emphasize this.

However, the assumption that pulmonary edema resulted from excess total body fluid may not be universally true. Most chronic CHF patients who are well-managed are euvolemic or even slightly dehydrated, and most incidences of acute pulmonary edema occur in the early morning hours or during sleep, when oral fluid intake is lowest. Many factors figure into the syndrome of pulmonary edema, principally the changes that take place in the heart as a result of chronic hypertension (cardiac remodeling—changes in the size, shape and function of a chamber of the heart) leading to either systolic or diastolic heart failure. Inadequate cardiac output leads to activation of the renin/angiotensin/aldosterone system (RAAS), which results in sodium and water retention, but this does not necessarily mean the patient is overhydrated.⁵

Acute pulmonary edema, therefore, may likely be less of a fluid volume problem than a fluid distribution problem. There may be no excess accumulation of fluid needing to be diuresed; it is simply in the wrong place and needs to be distributed properly. Some patients are overhydrated, but it is difficult to determine that by physical examination. At any rate, diuretics are now seen as an intervention best saved for those patients who do not respond to nitroglycerine.⁶

Since APE is a volume distribution problem, administration of furosemide provides no immediate benefit for most patients. Administration of furosemide carries the potential for hypokalemia, arrhythmias and increased systemic vascular resistance through enhancement of the RAAS, all of which may be deleterious to the acute CHF patient. Administration of furosemide to patients who really have COPD or pneumonia, rather than APE, can be especially harmful.

Evolution in APE Treatment

In recent years, intravenous administration of morphine sulfate and furosemide for acute pulmonary edema has given way to aggressive administration of nitrates. Prehospital administration of intravenous nitroglycerine infusion and graduated dosing protocols, allowing much higher doses of sublingual nitroglycerin in severely hypertensive patients (often doses of 1.2 grams or more for patients with systolic BP > 170), have proven highly effective at reversing acute pulmonary edema.

In one comparison of prehospital APE protocols, the study authors concluded that nitroglycerine alone was beneficial, while concomitant administration of morphine and furosemide provided no added benefit, and in some cases were harmful.⁶

Non-invasive positive pressure ventilation (NIPPV), or as it was once called, CPAP, has long been an effective adjunct in the ED and ICU for emergent treatment of acute pulmonary edema, but until recent years the devices were too expensive and complex to see much prehospital use. However, recent technological advances have resulted in affordable mechanical NIPPV flow generators, which are easy to use and rugged enough for prehospital use. There are even a wide variety of disposable NIPPV/CPAP systems specifically designed for EMS.

Aggressive administration of nitroglycerine, coupled with the rapid proliferation of prehospital NIPPV, has resulted in far less need for morphine and furosemide in treatment of acute CHF. While morphine still has a place as an effective analgesic, furosemide has been pushed to the back of the drug box to gather dust until it reaches its expiration date. Increasingly, EMS systems are relegating furosemide to medical command order only, or removing it from protocols entirely.

New Treatments on the Horizon

While current prehospital treatment of acute CHF, even in those patients suffering from volume overload, focuses on vasodilation with nitrates and alveolar recruitment with NIPPV, there are diagnostic tools and treatment options on the horizon that may creep into prehospital care.

ACE inhibitors such as captopril have shown promise in the emergent treatment of acute CHF, and sublingual captopril given in conjunction with nitroglycerine has been shown to significantly reduce APE distress scores within 40 minutes of administration.³

Administration of furosemide first requires diagnosis of volume overload, which usually requires laboratory testing of renal function and B natriuretic peptide (BNP). BNP is secreted by the myocardial muscle cells in response to excessive stretching of heart muscle cells, and is a definitive diagnostic indicator for congestive heart failure. Measurement of BNP is vital in differentiating CHF from pneumonia or COPD exacerbation.

While traditional laboratory testing is out of the reach of almost all EMS systems, technological advances have resulted in small and rugged point-of-care test meters capable of rapidly yielding quantitative lab results, including those for BNP and renal function. The only issue now is price, and those are steadily falling.

Is There Still a Place for Furosemide?

Diuresis is still indicated for CHF patients suffering from volume overload, so it is unlikely furosemide will disappear entirely. However, while a certain percentage of acute pulmonary edema patients suffer from volume overload, that percentage is fairly small, and treatment with nitrates and NIPPV is usually sufficient to stabilize the patient in the prehospital realm.

Proper diagnosis of volume overload requires laboratory testing beyond the capability of most EMS systems, and misdiagnosis of acute CHF can be disastrous with furosemide in the armamentarium. As always, a thorough history and assessment are the keys to choosing the proper treatment. Pulmonary crackles on auscultation and moist skin can just as easily be pneumonia as acute CHF, and vasodilation and diuresis in these patients can yield disastrous results. More than anything else, the presence of profound hypertension and orthopnea in a patient with severe respiratory distress point to acute pulmonary edema. If your patient isn’t hypertensive and his history doesn’t point to volume overload, it’s best to leave the furosemide in the box and let the ED administer it when they have a better diagnosis.

Or better yet, take furosemide out of the box entirely.

References

1. Fuster V, Alexander RW, O’Rourke, et al. Diagnosis and management of heart failure. Hurst’s The Heart 11^th ed. 723–62.

2. Mosesso, Jr. VN, Dunford J, Blackwell T, Griswell JK. Prehospital therapy for acute congestive heart failure: state of the art. Prehosp Emerg Care 7(1):13–23, 2003.

3. Bertini G, Giglioli C, Biggeri A, et al. Intravenous nitrates in the prehospital management of acute pulmonary edema. Ann Emerg Med 30:493–9, 1997.

4. Sacchetti AD, Harris RH. Acute cardiogenic pulmonary edema. What’s the latest in emergency treatment? Postgrad Med 103:145–66, 1998.

5. Sacchetti A, Ramoska E, Moakes ME, McDermott P, Moyer V. Effect of ED management on ICU use in acute pulmonary edema. Am J Emerg Med 7:571–4, 1999.

6. Fuster V, Alexander RW, O’Rourke, et al. Diagnosis and management of heart failure. Hurst’s The Heart 11^th ed. 723–62.

7. Tintinalli, Congestive heart failure and pulmonary edema. Emergency Medicine 7:405–13.

8. Hoffman JR, Reynolds S. Comparison of nitroglycerin, morphine and furosemide in treatment of presumed prehospital pulmonary edema. Chest 92:586–93, 1987.

Steven “Kelly” Grayson, NREMT-P, CCEMT-P, is a critical care paramedic for Acadian Ambulance in Louisiana. He has spent the past 14 years as a field paramedic, critical care transport paramedic, field supervisor and educator. He is a former president of the Louisiana EMS Instructor Society and board member of the Louisiana Association of Nationally Registered EMTs. He is a frequent EMS conference speaker and the author of the book En Route: A Paramedic’s Stories of Life, Death, and Everything In Between, and the popular blog A Day in the Life of An Ambulance Driver.

William E. (Gene) Gandy, JD, LP, has been a paramedic and EMS educator for over 30 years. He has implemented a two-year associate’s degree paramedic program for a community college, served as both a volunteer and paid paramedic, and practiced in both rural and urban settings and in the offshore oil industry. He has testified in court as an expert witness in a number of cases involving EMS providers and lectures on medical/legal aspects of EMS. He lives in Tucson, AZ.